Scoliosis, or lateral curvature of the spine, can occur as congenital type scoliosis or as familial or idiopathic type scoliosis (D'Ambrosia 1986), can result from the neuromuscular effects of a spinal cord injury (Dearolf 1990), or can result from illnesses causing neuromuscular weakness such as muscular dystrophy (Galasko 1933, Beals 1973). Whatever the cause, scoliosis is a major complication which hampers rehabilitation by impairing the body's skeletal support, and which compromises vital functions such as breathing and circulation by altering thoracic and abdominal geometry (D'Ambrosia 1986).
The lateral curvature of the spine in scoliosis is thought to be a consequence of insufficient and asymmetrical loading of the vertebrae. This is why scoliosis is highly prevalent under conditions that cause neuromuscular weakness. In fact mathematical modelling of the effects of weakened muscle contractility on vertebral loading can produce curves that are virtually identical to those observed in scoliosis patients (Schultz 1981, Takashima 1979, Ghista 1988).
Idiopathic scoliosis is the most common form (70%) of scoliosis. Although the specific mechanism is unknown (D'Ambrosia 1986), it is probable that neuromuscular abnormalities are also involved in idiopathic scoliosis (Maguire 1993, Kennelly 1993). This accounts for the aberrant prolongation of the spinal reflex activity for maintenance of posture observed in patients with idiopathic scoliosis (Maguire 1993). This reflex activity could not be ascribed to spinal curvature itself, since normal activity was measured in patients with similar but nonidiopathic curves. Also, the cross-sectional areas of paraspinal muscles, which support the spine, are unequal in idiopathic scoliosis (Kennelly 1993).
Because of the negative health effects and discomfort associated with scoliosis, it is important to reduce or eliminate scoliosis in an affected person. The standard practice is to try to correct the asymmetrical loading of the spine in scoliosis by braces which are surgically implanted or externally applied (D'Ambrosia 1986). Repeated electrical stimulation of weakened muscles has also been tried as a countermeasure (Schultz 1981). However, these modalities are invasive and cumbersome. Moreover, it is necessary to precisely determine the anatomical location at which to apply these corrective forces. If the forces are not correctly applied, this can actually worsen the scoliotic condition. Clearly alternatives, particularly of a pharmacological nature, are desirable. However, a difficulty in using pharmacological approaches is targeting the comparatively weaker musculature on the side of the spine which is convex. Unlike a systemically administered pharmaceutical, braces and electrical stimulation can, although with difficulty, be targeted to the specific region of treatment. In contrast, a systemically administered pharmaceutical would be expected to affect both the weaker and stronger sides equally or even favor the stronger side (Zeman II 1991), thus not to correct the asymmetry.
.beta..sub.2 -adrenoceptor agonists (.beta..sub.2 -agonists) are a class of compounds which have the same effect as the hormone epinephrine (adrenaline) binding to the adrenergic receptors found in smooth and skeletal muscle, nervous tissue, and bronchioles. Unlike epinephrine, .beta..sub.2 -agonists activate primarily the .beta..sub.2 receptor, not the .beta..sub.1 receptor, thus avoiding some of the "fight-or-flight" effects of epinephrine, such as increased heartrate. Because of their effect on bronchioles, .beta..sub.2 -agonists are well known for treating asthma.
It is also known that .beta..sub.2 -agonists can alter bone mass, probably due to increasing muscle tone (Zeman II 1991). .beta..sub.2 -agonists treatment also reduces loss of muscle mass and contractility in dystrophic (mdx) muscle whose fiber regeneration has been blocked (Zeman II 1994). Studies with the .beta..sub.2 -agonist clenbuterol show that .beta..sub.2 -agonists can partially oppose reductions in bone mineralization and muscle contractility that occur in response to surgical denervation (Zeman I 1987, Zeman II 1991, Agbenyega 1990). Clenbuterol has been used to increase strength in orthopedic patients following knee surgery (Maltin 1993). However, until the present invention, it has not been shown that these effects of .beta..sub.2 -agonists would have any applicability to spinal musculature, even less in the special situation of scoliosis where asymmetry is a problem.